Xiaflex Powder for injection

Xiaflex Powder for injection is a brand of medicine containing the active ingredient collagenase clostridium histolyticum.

Find out more about active ingredients.

Consumer medicine information (CMI) leaflet

Developed by the pharmaceutical company responsible for this medicine in Australia, according to TGA regulations.

XIAFLEX®
(Zi a flex)

Collagenase clostridium histolyticum - 900 micrograms powder and diluent for solution for injection


Consumer Medicine Information

What is in this leaflet

This leaflet answers some common questions about XIAFLEX.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you having XIAFLEX against the benefits they expect it will have.

If you have any concerns about this injection, ask your doctor, nurse or pharmacist.

Keep this leaflet. You may need to read it again.

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What XIAFLEX is used for

XIAFLEX is used for the treatment of Dupuytren’s contracture in adult patients with a palpable cord.

Dupuytren’s contracture is a disease that causes your finger(s) to bend inward. This bending is called a contracture and is caused by the abnormal formation of a cord(s) containing collagen under your skin.

For many people, a contracture causes significant difficulties with performing everyday tasks like driving, shaking hands, playing sports, opening jars, typing or holding objects.

How it works

XIAFLEX is injected directly into the palpable cord(s) by your doctor and works by breaking down the collagen in the cord(s) and thereby helps to remove the cause of your contracture so that your finger(s) can straighten.

The active substance is collagenase clostridium histolyticum, and is naturally produced by a bacterium named Clostridium histolyticum.

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Before you are given XIAFLEX

When you must not be given it

  • you must not receive XIAFLEX within 7 days of the last dose of your anticoagulation medicine. One exception is the use of up to 150mg daily dose of acetylsalicylic acid (also called aspirin, a substance present in many medicines used to prevent blood clotting) which can be taken.

Do not have XIAFLEX if you have an allergy to:

  • collagenase clostridium histolyticum or any of the ingredients listed at the end of this leaflet

Please consult a doctor immediately if you experience any signs or symptoms of a serious allergic reaction:

  • wide spread redness or rash,
  • swelling of the face, lips, throat or other parts of the body,
  • tightness in the chest, shortness of breath or difficulty breathing.

Do not use XIAFLEX in children under 18 years of age. There is not enough information at present to recommend use of XIAFLEX in children.

Do not use XIAFLEX after the expiry date printed on the pack.

Do not use XIAFLEX if the packaging is torn or shows signs of tampering.

If you are not sure whether you should have XIAFLEX, talk to your doctor or pharmacist.

Before you are given this medicine, make sure your doctor knows:

  • if you are pregnant or intend to become pregnant. There is no experience in the use of XIAFLEX in pregnant women therefore the use of XIAFLEX is not recommended in pregnancy, and treatment should be postponed until after pregnancy.
  • if you are breastfeeding
  • if you have a history of problems with the normal clotting of your blood or if you are taking any medicines to help control the normal clotting of your blood (known as anticoagulation medicines)
  • you are taking or have recently taken anthracyclines/anthraquinone derivatives such as doxorubicin and some tetracycline antibiotics such as doxycycline used to treat infections
  • any medicines obtained without a prescription (pharmacy or health food store).

Tell your doctor if you have allergies to:

  • any other medicines
  • any other substances, such as foods, preservatives or dyes

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines and XIAFLEX may interfere with each other.

Tell your doctor or pharmacist if you are using any medicine to thin your blood such as warfarin, clopidogrel or dabigatran. Some people refer to anticoagulation medicine as “blood thinners”. If you are not sure, please check with your doctor or pharmacist.

XIAFLEX must not be given within 7 days of the last dose of your anticoagulation medicine, One exception is the use of up to 150mg daily dose of acetylsalicylic acid (also called aspirin, a substance present in many medicines used to prevent blood clotting) which can be taken.

Tell your doctor of pharmacist if you are taking or have recently taken anthracyclines/ anthraquinone derivatives such as doxorubicin, and some tetracycline antibiotics such as doxycycline used to treat infections. XIAFLEX should not be given within 14 days of receiving tetracycline antibiotics.

These medicines may be affected by XIAFLEX, or may affect how well it works. (You may need different amounts of these medicines, or you may need to take different medicines.) Your doctor or pharmacist will advise you and decide whether or not to give the Injection.

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How XIAFLEX is given

Your doctor will perform all injections of XIAFLEX. XIAFLEX should only be used by an approved practitioner who will be able to display (or show you) such an authorisation.

This medicine must only be injected into the collagen cord in your hand by your doctor. Up to two cords or two affected joints in the same hand can be injected at the same time during a treatment visit. Two palpable cords affecting two joints may be injected or one palpable cord affecting two joints in the same finger may be injected at two locations during a treatment visit.

Your doctor will take care to avoid injecting into tendons, nerves or blood vessels.

Incorrect injection into tendons, nerves or blood vessels may result in bleeding or damage and possible permanent injury to these structures.

If your cord(s) to be treated is attached to the skin, you are at higher risk of the skin splitting or tearing during the finger(s) extension procedure following the injection of XIAFLEX. This will usually be treated by applying a dressing. In severe cases a skin graft may be required.

How much is given

Each vial of XIAFLEX and sterile solvent for reconstitution should only be used for a single injection. If cords of two affected joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection.

The recommended dose of your prescribed medicine is 0.58mg.

The total volume of the injection depends on the joint(s) being treated.

Your doctor will carefully select an area where the collagen cord(s) is best accessible and will proceed with the injection into the cord(s).

If you take too much (overdose)

As this product is administered to you by your doctor it is very unlikely that you will be given an incorrect dosage. In the unlikely event that your doctor administers a higher dosage than recommended, you may experience an increase in the severity of possible side effects especially reactions at the injection site listed under “Side effects” in this leaflet.

You can telephone your doctor or the Poisons Information Centre on 13 11 26 for advice on overdose management.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Clinical study experience with XIAFLEX is currently limited to up to 3 injections per cord at approximately 4 weeks interval.

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After having XIAFLEX

Things you must do

Be sure to ask your doctor when you can resume normal activities after treatment with XIAFLEX.

After the injection, your doctor will place a dressing on your hand. You must limit motion of the treated finger(s) for a day and it is not uncommon for the finger(s) to straighten on its own for some patients.

Until advised by your doctor, do not flex or extend the fingers of the injected hand.

Do not attempt to disrupt the injected cord(s) by self-manipulation at any time.

Elevate the injected hand as much as possible until bedtime.

Your doctor will ask you to return 24 to 72 hours after your injection to attempt to extend your finger(s) to straighten it.

Following extension of your finger, your doctor will fit you with a splint to wear at bedtime for up to 4 months.

It is recommended to avoid strenuous activities of your treated hand until instructed further by your doctor.

Your doctor may recommend you perform a series of finger flexion and extension exercises several times a day for several months when you are ready.

Keep follow-up appointments with your doctor.

If your finger(s) is/are still not able to straighten during a follow-up visit with your doctor, you may need additional treatments with XIAFLEX which may be administered approximately 4 weeks after the first treatment.

Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.

If the disease has resulted in multiple contractures, additional cords maybe treated at other treatment visits approximately 4 weeks apart as determined by your doctor.. ).

Tell your doctor immediately if:

  • Symptoms of infection (fever, chills, increased redness or swelling) appear
  • Symptoms of tendon rupture (trouble bending the finger after swelling goes down or altered sensation in the treated finger) appear.

Tell your doctor if symptoms of musculoskeletal syndrome (joint or muscle pain, joint stiffness, shoulder stiffness, hand swelling, fibrosis of the palms, and thickening or nodule forming of tendons) appear.

Serious allergic reactions and musculoskeletal syndrome are rare but serious side effects which require immediate medical attention.

Things to be careful of

Be careful driving or operating machinery until you know how XIAFLEX affects you. Swelling and pain which may impair the use of the treated hand and dizziness, numbness or altered sensation, and headache have been reported as side effects immediately after injection of XIAFLEX.

You must avoid potentially hazardous tasks such as driving or using machines until it is safe to do so or as advised by your doctor.

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Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well after having XIAFLEX. Like all medicines, XIAFLEX can cause side effects, although not everybody gets them.

Most of the side effects that occurred in the clinical studies were mild or moderate in severity and were localised to the hand treated.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

Very common:

  • reactions at the injection site like bleeding, pain, swelling, tenderness and bruising
  • itching in the hand or skin
  • feeling of pain in the hand, wrist or arm
  • swollen or enlarged glands near the elbow or under the arm
  • swelling in the hand or arm
  • blood blister
  • skin wound at the site of injection

Common side effects:

  • reactions at the injection site like pain, warmth, swelling, presence of a blister, redness of skin and/or skin rash
  • painful glands near the elbows or under the arm
  • joint swelling and pain
  • muscle pain or stiffness
  • burning sensation, partial loss of sensitivity, feeling of “pins and needles” or numbness
  • dizziness, headache, nausea
  • increased perspiration

These are the more common side effects of XIAFLEX. Mostly these are mild and short-lived.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

You may experience serious side effects which need urgent medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

Sudden signs of allergy such as:

  • widespread redness or rash,
  • swelling of the face, lips, throat or other parts of the body,
  • tightness in the chest, shortness of breath or difficulty breathing.

Contact your doctor if you have trouble bending the injected finger(s) after the swelling has subsided as it may be a symptom of tendon rupture.

These are very serious side effects. You may need urgent medical attention or hospitalisation.

As with any non-human protein medical product, the potential long term risk of autoimmune disease cannot be excluded.

All of these side effects are rare.

Other side effects not listed above may occur in some patients. Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

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Storing XIAFLEX

XIAFLEX is usually stored in the doctor’s surgery or clinic, or at the pharmacy. However, if you need to store XIAFLEX at home:

  • Keep out of the reach and sight of children.
  • Keep XIAFLEX in the original pack until it is time for it to be given.
  • Keep it in the refrigerator, between 2°C and 8°C. Do not freeze XIAFLEX.

After reconstitution, the medicine can be used immediately. Alternatively, reconstituted XIAFLEX can be kept at ambient room temperature (20ºC-25ºC) for up to one hour or refrigerated at 2ºC-8ºC for up to 4 hours prior to administration. If refrigerated, the reconstituted solution must be allowed to return to ambient room temperature (20ºC-25ºC) for approximately 15 minutes before use.

Your doctor must not use XIAFLEX if the reconstituted solution is discolored or contains particles.

The reconstituted solution must be clear, colourless with no lumps or flakes or particles.

Your doctor will take care of storing, handling and disposing of XIAFLEX.

Medicines must not be disposed of via wastewater or household waste. These measures will help to protect the environment.

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Product description

What it looks like

XIAFLEX is supplied as a white powder in a 3 mL clear glass vial with rubber stopper, aluminium seal and flip-off plastic cap.

The 3 mL diluent that is used to dissolve the powder is supplied as a clear liquid in a 5 mL clear glass vial with rubber stopper, aluminium seal and flip-off plastic cap.

XIAFLEX is supplied in a single use pack containing 1 vial of XIAFLEX powder and 1 vial of 3 mL diluent.

Ingredients

Each vial of XIAFLEX 900 micrograms Powder contains:

Active ingredients:
collagenase clostridium histolyticum

Inactive ingredients:

  • sucrose,
  • trometamol,
  • hydrochloric acid

Each vial of Diluent contains:

  • Ingredients
    - calcium chloride,
    - sodium chloride,
    - water for injection

Manufacturer/ Distributor/ Supplier

XIAFLEX is supplied in Australia by:
Actelion Pharmaceuticals Australia Pty Ltd.
Suite 6/13b Narabang Way
BELROSE NSW 2085

Australian Registration Number:
XIAFLEX - AUST R 199584

This leaflet was prepared in January 2016.

The following information is intended for medical or healthcare professionals only:

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Instructions for use and handling

1. Preparation - Reconstitution procedure

The single dose vial containing XIAFLEX powder and the single dose vial containing the diluent for solution for injection for reconstitution must be refrigerated. Prior to use, the vial containing XIAFLEX powder and the vial containing the diluent for solution for reconstitution must be removed from the refrigerator and allowed to stand at room temperature for at least 15 minutes and no longer than 60 minutes.

Each vial of XIAFLEX and sterile solvent for reconstitution should only be used for a single injection. If two cords of affected joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection.

Using an aseptic technique, the following procedure for reconstitution must be followed:

  1. Confirm the joint(s) to be treated (metacarpophalangeal [MP] or proximal interphalangeal [PIP]) as the volume of diluent required for reconstitution is determined by the type of joint (PIP joint requires a smaller volume for injection).
  2. Remove the flip-off plastic caps from the vials and swab the rubber stopper and surrounding surface of the vial containing XIAFLEX powder and the vial containing the diluent for reconstitution with sterile alcohol (no other antiseptics must be used).
  3. Use only the supplied diluent for reconstitution; it contains calcium which is required for the activity of XIAFLEX powder. Using a sterile syringe calibrated with 0.01 mL graduations, withdraw the appropriate amount of diluent supplied in order to deliver as follows:
  • 0.39mL of diluent for cords affecting a MP joint or
  • 0.31mL of diluent for cords affecting a PIP joint
  1. Inject the diluent slowly into the sides of the vial containing the XIAFLEX powder. Do not invert the vial or shake the solution. Slowly swirl the solution to ensure that all of the lyophilised powder has gone into solution. Remove and discard the syringe and needle used for reconstitution.
  2. Inspect the solution visually for particulate matter and discolouration prior to administration. The reconstituted solution of XIAFLEX injection must be clear. If the solution contains particles, is cloudy or discoloured, do not inject it.
  3. Reconstituted XIAFLEX injection can be kept at ambient room temperature (20ºC-25ºC) for up to one hour or refrigerated (2ºC-8°C) for up to 4 hours prior to administration.

If the reconstituted XIAFLEX solution is refrigerated, allow this solution to return to room temperature for approximately 15 minutes before use.

2. Injection procedure

Ensure appropriate equipment is available to address any severe local or systemic allergic reactions including potential for anaphylaxis that may occur following injection.

Administration of a local anaesthetic prior to XIAFLEX injection is not recommended, as it may interfere with proper placement of the injection.

  1. Reconfirm the cord(s) to be injected. The site chosen for injection must be the area where the contracting cord is maximally separated from the underlying flexor tendons and where the skin is not intimately adhered to the cord.
  2. Prepare the skin with an antiseptic and allow it to dry.
  3. Using a sterile, hubless syringe with 0.01mL graduations and a permanently fixed, 26 or 27 gauge, 12 or 13mm needle (not supplied), withdraw the adequate volume of reconstituted solution for a 0.58mg dose of XIAFLEX required for injection to deliver:
    - 0.25 of reconstituted XIAFLEX for cords affecting a MP joint or
    - 0.20 of reconstituted XIAFLEX for cords affecting a PIP joint.

    Note that injection volume for delivery of a 0.58 mg dose is less than the total volume of diluent used for reconstitution. The entire reconstituted XIAFLEX solution contains 0.9 mg of XIAFLEX. Any reconstituted XIAFLEX solution remaining in the vial after the injection should be discarded.
  4. Use caution with cords as they approach the PIP flexion crease area. If injecting into a cord affecting the PIP joint of the fifth (little) finger, care must be taken to inject as close to the palmar digital crease as possible and not to insert more than 2mm to 3mm in depth. For PIP joints do not inject more than 4 mm distal to the palmar digital crease.
  5. When administering two injections in the same hand during a treatment visit, begin with the affected finger in the most ulnar aspect of the hand and continue toward the radial aspect (eg, fifth finger to index finger). Within each finger, begin with the affected joint in the most proximal aspect of the finger and continue toward the distal aspect (eg, MP to PIP).
  6. With your non-dominant hand, secure the patient’s hand to be treated while simultaneously applying tension to the cord. With your dominant hand, place the needle into the cord, using caution to keep the needle within the cord. Avoid having the needle tip pass completely through the cord to help minimise the potential risk of XIAFLEX injection passing into tissues other than the cord. After needle placement, if there is any concern that the needle is in the flexor tendon, apply a small amount of passive motion at the distal interphalangeal (DIP) joint. If insertion of the needle into a tendon is suspected or paresthesia is noted by the patient, withdraw the needle and reposition it into the cord. If the needle is in the proper location, there will be some resistance noted during the injection procedure. See Figure 1 for an illustration of the injection technique.
  7. After confirming that the needle is correctly placed in the cord, inject approximately one-third of the dose.
  8. Next, keeping the needle under the skin at all times, withdraw the needle tip from the cord and reposition it in a slightly more distal location (approximately 2-3 mm) to the initial injection in the cord and inject another one-third of the dose.
  9. Again keeping the needle under the skin at all times, withdraw the needle tip from the cord and reposition it a third time proximal to the initial injection (approximately 2-3 mm) and inject the final portion of the dose into the cord (see Figure 2).
    The figures 1 and 2 are for illustrative purposes only and may not be representative of the precise location of anatomical structures in an individual patient

  1. Repeat the injection procedure to the remaining cord.
  2. Wrap the patient’s treated hand with a soft, bulky, gauze dressing.
  3. Observe the patient for at least 20 minutes following injection and be prepared to address any severe local or systemic allergic reactions including potential for anaphylaxis that may occur following injection.
  4. Discard the unused portion of the reconstituted solution and diluent after injection. Do not store, pool, or use any vials containing unused reconstituted solution or diluent.
  5. Patients should be instructed:
  • To remove all jewellery from the hand to be treated.
  • Not to flex or extend the fingers of the injected hand to reduce extravasation of XIAFLEX injection out of the cord.
  • Not attempt to disrupt the injected cord by self manipulation at any time.
  • To elevate the injected hand as much as possible until bedtime.
  • To promptly contact their doctor if there is evidence of infection (e.g. fever, chills, increasing redness or oedema) or trouble bending the finger after the swelling goes down (symptoms of tendon rupture).
  • To return to see their physician the next day for an examination of the injected hand and a possible finger extension procedure to disrupt the cord.

3. Finger extension procedure

  1. At the follow-up visit 24 to 72 hours after the injection, determine if the contracture has resolved. If the cord(s) contracture remains, the finger extension procedure will be performed in an attempt to disrupt the cord(s). If cords of two affected joints in one finger were treated, perform the finger extension procedure on the cord affecting the MP joint before performing the procedure on the cord affecting the PIP joint.
  2. Local anaesthesia may be used, if needed, during the finger extension procedure. Avoid direct pressure on the injection site as it will likely be tender. Care should be taken during release of contracture, as some patients may experience skin splitting. If this occurs, cover the area with gauze and apply gentle pressure until bleeding stops. Standard wound care with regular dressings should be applied.
  3. While the patient’s wrist is in the flexed position, apply moderate stretching pressure to the injected cord by extending the finger for approximately 10 to 20 seconds. For cords affecting the PIP joint, perform the finger extension procedure when the MP joint is in the flexed position.
  4. If the first finger extension procedure does not result in disruption of the cord(s), a second and third attempt can be performed at 5- to 10-minute intervals. No more than 3 attempts per joint are recommended to disrupt a cord(s).
  5. If the cord(s) has/have not disrupted after 3 attempts of extension, a follow-up visit may be scheduled approximately 4 weeks after the injection. If, at that subsequent visit the contracted cord persists, an additional injection and finger extension procedure may be performed.
  6. Following the finger extension procedure(s) and fitting patient with a splint (with treated joint in maximum extension), patients should be instructed to:
  • Not perform strenuous activity with the injected hand until advised to do so.
  • Wear the splint at bedtime for up to 4 months.
  • Perform a series of finger flexion and extension exercises several times a day for several months.

Manufacturer/Distributor/ Supplier

XIAFLEX is supplied in Australia by:
Actelion Pharmaceuticals Australia Pty Ltd.
Suite 6
13b Narabang Way
BELROSE NSW 2085

Australian Registration Number:
XIAFLEX - AUST R 199584

This leaflet was prepared in January 2016.

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CMI provided by MIMS Australia, March 2016  

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